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Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 343 records · Page 19Linked to original sources

Type I collagen synthesis by corneal endothelial cells modulated by polymorphonuclear leukocytes.

When primary corneal endothelial cells were grown in polymorphonuclear leukocyte (PMN)-conditioned medium, a minor population of cells acquired fibroblastic morphology. Such modulated endothelial cells supported by PMN-conditioned medium grew much faster than the major nonresponding polygonal endothelial cell. Upon serial passages, the modulated endothelial cells became the dominant cell type and eventually formed a homogeneous fibroblastic culture. At the same time, phenotypic changes of collagen were observed. The primary endothelial cells grown in PMN-conditioned medium, consisting of responding elongated cells and nonresponding polygonal endothelial cells, produced predominantly type IV collagen with type III collagen as a minor component. As cells were subcultured and fibroblastic cells became dominant, type IV collagen synthesis was dramatically decreased and type I collagen synthesis was increased in parallel. When they reached the fully modulated stage, the cultures synthesized types I and III collagen, with type I accounting for 75-85% of the total. Type I collagen synthesized by the fibroblastic endothelial cells shared common characteristics with known type I collagen, such as migration behavior on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, CNBr peptide profiles, and immunologic identity. Thus, PMNs apparently contribute to the modulation of corneal endothelial cells, causing them to acquire characteristics of fibroblasts, cell multilayering, and deposition of interstitial extracellular matrix composed predominantly of interstitial type I collagen.

Animals↗

Use of different derivatives of D-Val-Leu-Arg for studying kallikrein activities in cat submandibular glands and saliva.

Glandular kallikrein shows a special selectivity for D-Val-Leu-Arg-4-methoxy-2-naphthylamide in comparison with other potential oligopeptide substrates and it provides a useful histochemical substrate, although the reaction may not always be specific. However, in cat submandibular saliva, a biochemical assay using the closely related D-Val-Leu-Arg-7-amino-4-trifluoromethylcoumarin (AFC) as substrate, which affords more sensitive detection, showed that soya bean trypsin inhibitor causes no inhibition. This indicates that there are unlikely to be contaminating enzymes competing for the substrate in this body fluid. Support for this observation has been gained by the useful new enzyme overlay membrane technique for fluorescent assessment of reactive bands of enzymes after isoelectric focusing, using membranes of cellulose acetate impregnated with D-Val-Leu-Arg-AFC. Comparison of results after isoelectric focusing of purified cat submandibular kallikrein with samples of cat submandibular saliva confirmed that the substrate is monospecific for kallikrein in saliva of the cat. This knowledge has enabled us to start assessing the dynamics of the secretion of kallikrein by the gland. Testing individual drops of saliva has shown that an amazingly rapid mobilization of kallikrein occurs in high concentrations on sympathetic nerve stimulation. The corresponding oligopeptide-based inhibitor D-Val-Leu-Arg-chloromethyl ketone was found to be strongly inhibitory of the amidase reaction by kallikrein but showed a low specificity for kallikrein. Nevertheless, its effects have been tested in vivo by the intravascular route and it caused an increase in the resting salivary vascular resistance whether administered close-arterially or intravenously. Thus, it would seem that a kallikrein-like protease does influence the background tone in the vessels and the source of this enzyme is thought to be mast cells.

Amino Acid Chloromethyl Ketones↗

Stress management training as a prevention program for heavy social drinkers: cognitions, affect, drinking, and individual differences.

The effectiveness of cognitive-affective stress management training (SMT) as a drinking reduction program for heavy social drinking college students was investigated. The SMT package included muscle relaxation and meditation training, cognitive restructuring, and coping skill rehearsal during induced affect. Treated and control subjects rated the frequency and intensity of their anxiety, anger and depression and recorded their alcohol consumption on a daily basis over a 6-month period. SMT significantly reduced posttreatment daily anxiety ratings and was associated with changes in four of ten irrational beliefs and a shift toward more internal locus of control in treated subjects. Reduction in anxiety was no longer evident at the 2 1/2- and 5 1/2-month follow-ups. The men in the SMT group showed a significant decrease in daily drinking rates at posttreatment and at the 2 1/2-month follow-up, but drinking returned to baseline levels by 5 1/2 months for the group as a whole. However, significant improvement variance in daily moods and in drinking rates over all posttreatment periods was accounted for by individual difference variables in the trained subjects but not in the control group, suggesting that these cognitive, personality, and social support variables are associated with response to stress management training. Implications of these results for future prevention research are discussed.

Adult↗

In vivo transillumination biomicroscopy and photography of meibomian gland dysfunction. A clinical study.

Meibomian gland transillumination biomicroscopy and infrared photography were performed on 18 patients with clinically evident meibomian gland dysfunction (MGD) and dermatologic rosacea, 22 patients having MGD without evidence of dermatologic rosacea, and 15 unaffected individuals who served as controls. All patients having clinical signs of MGD demonstrated morphologic abnormalities of their meibomian glands by transilluminated biomicroscopy. Patients without dermatologic rosacea were noted to have varying degrees of gland distortion. Moreover, infrared photography documented a loss of the normal grape-like clusters of dark spots that represent the gland, suggesting a loss of glandular acini. Patients with dermatologic rosacea had more severe alterations, including marked distortion and loss of normal gland anatomy. There were no such abnormalities in clinically unaffected individuals. These data demonstrate that transilluminated biomicroscopy and infrared photography have the ability to identify a spectrum of morphologic alterations of the meibomian glands in MGD patients. The authors suggest that these techniques could be used to classify clinical MGD based upon the presence or absence of identifiable meibomian gland abnormalities.

Eyelid Diseases↗

Effect of substrate concentration, product concentration, and peptides on the in vitro hydrolysis of model ester prodrugs by corneal esterases.

The corneal epithelial fraction of albino rabbits with butyrylcholinesterase-like activity, which was purified by gel filtration chromatography, was studied with respect to its susceptibility to substrate and product inhibition using a pH-stat method. 1- and 2-Naphthyl acetates were used as model ester prodrugs. It was found that the hydrolytic rate of 1- and 2-naphthyl acetates at 1.2 mM was only 53% and 42% of that at 0.06 mM, respectively, suggesting that increasing the dose of an ester prodrug does not necessarily result in a proportional increase in its hydrolytic rate. Product inhibition (by 1- and 2-naphthol) was evident only at a product concentration at least equal to the substrate concentration, suggesting that, at the therapeutic concentrations of an ester prodrug, product inhibition is probably insignificant. Substrate and product inhibition did not appear to occur at the enzyme's active site. Moreover, the neuropeptides enkephalins and their hydrolytic fragments were found to inhibit the hydrolysis of 1-naphthyl acetate, albeit less effectively than compounds such as 1- and 2-naphthol.

Animals↗

Ocular esterase composition in albino and pigmented rabbits: possible implications in ocular prodrug design and evaluation.

A methodology was developed to determine the proportion of acetyl- (AChE) and butyrylcholinesterase (BuChE) in the albino and pigmented rabbit eye. It was found that BuChE contributed over 75% of the cholinesterase activity in all the ocular tissues but the corneal epithelium of the albino rabbit. This esterase was principally responsible for the parabolic chain length dependence of ocular hydrolysis of model naphthyl ester prodrugs reported previously. In contrast, when incubated with AChE, the rate of hydrolysis of these esters decreased monotonically with increasing ester chain length. Together these findings suggest that esters whose chain length exceeds 4 carbons will be hydrolyzed primarily by BuChE. It is suggested that the dominance of BuChE in ocular tissues is another factor which merits consideration in the design and evaluation of ocular ester prodrugs.

Acetylcholinesterase↗

Prevalence of Campylobacter jejuni in felidae in Baton Rouge, Louisiana.

A prevalence study revealed Campylobacter jejuni in rectal swabs of 1% of a sample of 430 domestic cats and from one species of 15 zoo felines which were examined. There was no correlation between age, presence of diarrhea, source of sample (animal shelter, veterinary clinic, domestic pet) and the isolation of C. jejuni. A controlled exposure trial confirmed that fecal shedders can transmit infection to susceptible contacts which subsequently demonstrate transient diarrhea. Infected cats show a variable pattern of excretion of the organism which could result in failure to determine C. jejuni status based on a single examination.

Animals↗

Theophylline-lithium interaction.

The effect of steady state therapeutic theophylline serum levels on lithium renal clearance was investigated. Group mean lithium renal clearances and serum lithium levels varied in predicted fashion. Individual variability in these parameters was significant. Clinical implications are considered and management suggestions made.

Adult↗

In vitro contractility of avascular corneal wounds in rabbit eyes.

Contraction of corneal wounds has been the topic of recent speculation, particularly in reference to regression of corneal flattening following radial keratotomy. In an animal model of corneal wound fibroplasia, we offer the first demonstration of in vitro contractility by avascular corneal wound tissue. Three millimeter diameter full-thickness corneal trephine wounds were made in 17 New Zealand white rabbit eyes. The animals were killed and specimens were extracted 3-4 wk postinjury. Contractile responses of corneal wounds were measured on a microdynagauge force transducer. When exposed to serotonin, epinephrine or norepinephrine corneal wounds showed contractions reaching maximum force of 20-100 mg with a peak response obtained within 5-10 min and persisting several hours. Normal corneas did not respond to any agent. All normal iris muscle specimens contracted to acetylcholine exhibiting peak responses of 30-60 mg of force within 5 sec decaying over the following 10-20 min. This is different from corneal wounds which fail to respond to acetylcholine (P less than 0.005). These data suggest that avascular corneal wounds possess contractile properties.

Animals↗

Results of penetrating keratoplasty for aphakic and pseudophakic bullous keratopathy.

We retrospectively studied 61 consecutive cases of penetrating keratoplasty performed for aphakic bullous keratopathy or pseudophakic bullous keratopathy. After keratoplasty, the mean visual acuities of both groups of patients improved significantly from preoperative levels (P less than .0001). One year after keratoplasty, 18 eyes had visual acuities of 20/40 or better. Twelve of the 24 eyes followed up for at least two years after surgery had visual acuities of 20/40 or better. The mean visual acuities for the eyes with aphakic bullous keratopathy and the eyes with pseudophakic bullous keratopathy were not significantly different at either one or two years after keratoplasty. Cystoid macular edema (11 eyes) and glaucoma (12 eyes) were the most common causes of visual acuities worse than 20/40. There were no significant differences in the incidences of these complications in the group with aphakic bullous keratopathy and in the group with pseudophakic bullous keratopathy. Intraocular lens removal did not significantly affect either visual acuity or macular complications after keratoplasty.

Aged↗

Response of esthesioneuroblastoma to chemotherapy. Report of five cases and review of the literature.

Five patients with advanced stage or metastatic esthesioneuroblastoma treated with chemotherapy are reported, and another eight cases found in the literature are reviewed. In this collective experience with chemotherapy in this disease, the authors found that 8 of 13 patients (62%) had an objective response to chemotherapy. The agents which may be active in this disease and the role of chemotherapy, particularly adjuvant therapy for patients presenting with advanced disease, are discussed.

Adolescent↗

Endothelial cell loss following radial keratotomy in a primate model.

The effect of radial keratotomy on the corneal endothelium of subhuman primates was studied by serial specular microscopy and histopathology. Fixed-frame analysis of specular micrographs of 13 operated eyes at one month after surgery revealed an endothelial cell loss of 13% (+/- 4%). Follow-up of all 13 eyes for six months disclosed no statistically significant progressive endothelial cell loss. Similarly, no significant loss could be demonstrated in five eyes followed up for 18 months and two eyes followed up four years after surgery. Variable frame analyses of specular micrographs of all 13 unoperated eyes followed up for six months also did not suggest progressive endothelial cell loss following radial keratotomy. Histopathology and ultrastructural studies of corneas undergoing radial keratotomy disclosed no abnormalities suggesting ongoing endothelial cell damage. These findings suggest that radial keratotomy produces an acute postoperative endothelial cell loss that is nonprogressive. Much longer term follow-up with larger numbers of subjects is necessary before the ultimate delayed effects of radial keratotomy on the endothelium can be determined.

Animals↗

Recent advances in protease research using synthetic substrates.

2-Naphthylamine, 4-methoxy-2-naphthylamine, 7-amino-4-methylcoumarin and 7-amino-4-trifluoromethylcoumarin and X peptides have become a useful tool to study proteases by a battery of complementary methods; they now include biochemistry, section biochemistry, location cytochemistry, ultracytochemistry and isoelectric focusing. By the use of these procedures we hope that more insight will be possible in the functional role of proteases in health and disease in the near future.

Animals↗